Synthesis of gem-Difluoroalkenes via a Sequence of Hydroboration and 1,2-Elimination of α,β-Unsaturated Carbonyls

Abstract

We reported a simple protocol for the synthesis of gem-difluoroalkenes via a reaction sequence of hydroboration and 1,2-elimination of α,β-unsaturated carbonyl substrates under mild conditions. Two steps of this method could be executed in one pot. The β-CF₂H- and β-CFH₂-α,β-unsaturated carbonyls can be obtained smoothly from the α,β-unsaturated gem-difluoroamide with NaH as the base and via a boration–1,2-elimination sequence.

Key words

gem-difluoroalkene - boration - 1,2-elimination - α,β-unsaturated carbonyls - fluoroalkene

Publication History

Received: 26 August 2020

Accepted after revision: 03 September 2020

Article published online:
14 October 2020

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• 11 Typical Procedure for the Synthesis of 4,4,4-Trifluoro-N-phenyl-3-(4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)butanamide (3a) The reaction mixture of α,β-unsaturated carbonyl substrate 1a (0.2 mmol), B₂pin₂ (2, 0.3 mmol, 1.5 equiv), CuCl (10 mol%), t-BuOLi (15 mol%), and i-PrOH (0.4 mol, 2.0 equiv) was stirred in THF (2.0 mL) at room temperature for 12 h. After the reaction was accomplished, the solvent was evaporated, and the crude mixture purified by flash chromatography on silica gel to afford the desired compound 3a in 92% yield. ¹H NMR (300 MHz, CDCl₃): δ = 8.15 (br, 1 H), 7.53–7.40 (m, 2 H), 7.33–7.18 (m, 2 H), 7.15–7.03 (m, 1 H), 2.80 (qd, J = 16.4, 7.9 Hz, 2 H), 2.23 (dd, J = 17.3, 10.1 Hz, 1 H), 1.26 (d, J = 7.6 Hz, 12 H). ¹³C NMR (75 MHz, MeOD): δ = 176.83, 137.86, 130.42 (d, J = 273.8 Hz), 130.25, 127.21, 121.97, 83.04, 33.17, 33.12, 25.41, 25.15. ¹⁹F NMR (282 MHz, CDCl₃): δ = –63.10. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₂₂BF₃NO₃: 344.1642; found: 344.1647.